Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms

Abstract

Huntington's disease is a progressive, degenerative disease characterized by abnormal body movements called chorea, and a reduction of various mental abilities. 3-Nitropropionic acid, an inhibitor of complex II of the electron transport chain, causes Huntington's disease-like symptoms in rodents. Recently, it has been reported that oxidative stress, which is one of the pathological hallmarks of various neurodegenerative disorders, also plays an important role in the pathogenesis of Huntington's disease. The present study was designed to investigate effects of resveratrol, an antioxidant with cyclooxygenase I inhibitory activity, in the 3-nitropropionic acid-induced model of Huntington's disease. Intraperitoneal administration of 3-nitropropionic acid (20 mg/kg for 4 days) caused significant loss of body weight, a decline in motor function (locomotor activity, movement pattern and vacuous chewing movements) and poor retention of memory. Repeated treatment with resveratrol (5 and 10 mg/kg, orally), once daily for a period of 8 days beginning 4 days prior to 3-nitropropionic acid administration, significantly improved the 3-nitropropionic acid-induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-nitropropionic acid administration significantly increased lipid peroxidation, nitrite levels, and depleted reduced glutathione levels, and decreased succinate dehydrogenase activity in the brains of rats. The results of the present study indicate that resveratrol (5 and 10 mg/kg, orally) significantly reversed 3-nitropropionic acid-induced motor and cognitive impairment, and that the beneficial effects of resveratrol might be attributed to its antioxidant activity.

Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease

“…Intriguingly, systemic treatment with Ppt for 5 days restored the weight loss and mitigated the behavior disorders in the 3-NP treated rats. Kumar et al have shown that antioxidative treatments restore behavioral disorders and antioxidative defense mechanisms in 3-NP treated animals [10,11,31] . In the CNS, cells are able to defend against oxidative stress using several resources, including vitamins, bioactive molecules, lipoic acid, enzymes (such as SOD, GSH, GPx, HO-1, and NQO1), and redox sensitive protein transcription factors (such as AP-1, Nrf2, and HSF) [32,33] .…”

“…Antioxidative drugs [20] and the overexpression of genes involved in attenuating oxidative stress showed significant neuroprotective effects against 3-NP-mediated neurotoxicity [11,31] . Ppt warrants attention as a potential anti-oxidative therapy for HD.…”

“…A large number of reports have demonstrated that panax ginseng possesses a number of beneficial effects in the CNS [1,[27][28][29][30][31][32][33][34][35][36] . Protopanaxtriol (Ppt) is a neuroprotective ginseng extract.…”

Effect of Resveratrol Supplementation on the Performance of Dogs in an Eight-Arm Radial Maze

“…Resveratrol, a plant-derived phytoestrogen, may minimise the deterioration in cognitive function associated with physical and chemical damage to the brain [1][2][3][4][5][6][7]. In rats and mice, resveratrol has been found to minimise the adverse brain and cognitive changes induced by neurologically damaging events such as streptozotocin-induced diabetes [1]; percussive cerebral trauma [2]; focal cerebral ischemia (stroke) [3]; oxidative stress caused by intracerebroventricular injection of streptozotocin [4] or cochinine [5]; and neurotoxic substances used to mimic Huntington's disease [6] and Parkinson's disease [7].…”

Grape Secondary Metabolites – Benefits for Human Health

“…One of the major mechanisms of toxin action is the induction of mitochondrial dysfunction via oxidative stress. Several studies reported the protection activity of resveratrol against this neurotoxin and suggested that it was its antioxidant properties that are responsible for the prevention of the functional effect of the toxin (Binienda et al, 2010;Kumar et al, 2006). Furthermore, some authors reported that the beneficial effect of resveratrol is through activation of SIRT1 (Howitz et al, 2003;Lagouge et al, 2006).…”